title: Myocardial expression of heat shock protein 70i protects early postoperative right ventricular function in cyanotic tetralogy of Fallot.
abstract: BACKGROUND
  Right ventricular dysfunction occurs after tetralogy of Fallot repair and may relate to greater myocardial vulnerability to ischemia-reperfusion injury in cyanotic patients. The inducible form of heat shock protein 70 (HSP-70i), a molecular chaperone, is upregulated in response to cellular stress and limits myocardial injury against ischemia-reperfusion. We evaluated the myocardial expression of HSP-70i and its relation to right ventricular function and clinical outcome in patients with tetralogy of Fallot undergoing corrective surgery.
  
  
  METHODS
  Twenty patients with tetralogy of Fallot were studied: 10 cyanotic (group Cy) and 10 noncyanotic (group noCy). Western blot was used to quantify HSP-70i from resected right ventricular outflow tract myocardium at baseline and subsequent ischemic time. Biventricular function was quantified by tissue Doppler echocardiography and compared with that of 15 age-matched healthy children. Postoperative systemic perfusion was assessed by mixed venous oxygen saturation, oxygen extraction ratio, and lactate.
  
  
  RESULTS
  Group Cy had thicker septum (median 0.85 vs 0.66 cm; P = .01) and longer crossclamp time (median 100.0 vs 67.5 minutes; P = .004). There were no difference in HSP-70i between groups at baseline (4.12 vs 3.44 relative optical density; P = .45) or subsequent ischemic time. Preoperative biventricular systolic function was reduced in patients with tetralogy compared with controls with further postoperative right ventricular impairment. Group Cy had higher troponin-I levels (median 16.5 vs 11.1 ng/mL; P = .04) and inotrope scores (14.0 vs 6.5; P = .05) but no differences in ventricular function, mixed venous oxygen saturation, oxygen extraction ratio, and lactate between groups. In group Cy, baseline HSP-70i correlated with better postoperative right ventricular function (rho = 0.80; P = .009), mixed venous oxygen saturation (rho = 0.68; P = .04), and oxygen extraction ratio (rho = -0.71; P = .03). These relationships were absent in group noCy.
  
  
  CONCLUSIONS
  The association of HSP-70i expression with improved right ventricular function and systemic perfusion suggests an important cardioprotective effect of HSP-70i in cyanotic tetralogy of Fallot.
authors.affiliation: Department of Cardiac Surgery, Royal Hospital for Sick Children, Yorkhill, Glasgow, United Kingdom.
authors.forename: Edward W K
authors.initials: EW
authors.lastname: Peng
authors.forename: David
authors.initials: D
authors.lastname: McCaig
authors.forename: James C S
authors.initials: JC
authors.lastname: Pollock
authors.forename: Kenneth
authors.initials: K
authors.lastname: MacArthur
authors.forename: Fiona
authors.initials: F
authors.lastname: Lyall
authors.forename: Mark H D
authors.initials: MH
authors.lastname: Danton
mesh_terms: D001784:Blood Gas Analysis; D015153:Blotting, Western; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016022:Case-Control Studies; D002675:Child, Preschool; D003490:Cyanosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism; D015150:Echocardiography, Doppler; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D007223:Infant; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012606:Scotland; D013771:Tetralogy of Fallot / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000378:metabolism; D015854:Up-Regulation; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016278:Ventricular Function, Right
chemical_list: D050884:HSP72 Heat-Shock Proteins; D019210:Troponin I